tbuckley/cabot-search huggingface dataset:
Impact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer
Authors: Matteo Lambertini, Marcello Ceppi, Richard A. Anderson, David A. Cameron, Marco Bruzzone, Maria Alice Franzoi, Claudia Massarotti, Sarra El-Abed, Yingbo Wang, Christophe Lecocq, Paolo Nuciforo, Rebecca Rolyance, Lajos Pusztai, Joohyuk Sohn, Maria Maddalena Latocca, Luca Arecco, Barbara Pistilli, Kathryn J. Ruddy, Alberto Ballestrero, Lucia Del Mastro, Fedro A. Peccatori, Ann H. Partridge, Cristina Saura, Michael Untch, Martine Piccart, Serena Di Cosimo, Evandro de Azambuja, Isabelle Demeestere
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment–induced gonadotoxicity. Patients and Methods: The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the “biological window” of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy). Results: The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33–42 years). AMH values at the 3 time points differed significantly ( P &lt;.001). At baseline, median AMH levels were 1.29 ng/mL (IQR, 0.56–2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median, 1.10 ng/mL; IQR, 0.45–2.09 ng/mL; P &lt;.001). At surgery, a larger significant decline in AMH levels was observed (median, 0.01 ng/mL; IQR, 0.01–0.03 ng/mL; P &lt;.001). Although the type of anti-HER2 treatment (trastuzumab and/or lapatinib) did not seem to impact the results, age and pretreatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk. Conclusions: This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.
Participation of Patients With Limited English Proficiency in Gynecologic Oncology Clinical Trials
Authors: Soledad Jorge, Shatreen Masshoor, Heidi J. Gray, Elizabeth M. Swisher, Kemi M. Doll
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Significant disparities exist in recruitment of minorities to clinical trials, with much of the prior literature focused on race/ethnicity only. Limited English proficiency (LEP) is a known barrier in healthcare that may also drive disparities in trial enrollment. We sought to determine participation rates in gynecologic oncology trials among patients with LEP and to explore barriers to their participation. Methods: In a retrospective cohort study, electronic health record data from &gt;2,700 patients treated over 2 years at one academic gynecologic oncology practice were abstracted and the primary exposure of having LEP was identified. The primary outcome was enrollment in a clinical trial. Demographic, financial, clinical, and healthcare access–related covariates were also abstracted and considered as potential confounders in a multivariable logistic regression model. Age, race, ethnicity, and insurance status were further examined for evidence of effect modification. In addition, a survey was administered to all gynecologic oncology research staff and gynecologic oncology providers (n=25) to assess barriers to research participation among patients with LEP. Results: Clinical trial enrollment was 7.5% among fluent English speakers and 2.2% among patients with LEP (risk ratio, 0.29; 95% CI, 0.11–0.78; P =.007), and remained significantly lower in patients with LEP after adjusting for the identified confounders of Hispanic ethnicity and insurance payer (odds ratio, 0.34; 95% CI, 0.12–0.97; P =.043). There was a trend toward race and LEP interaction: Asian patients were equally likely to participate in research regardless of language fluency, whereas White and Black patients with LEP were less likely to participate than non-LEP patients in both groups ( P =.07). Providers reported that the most significant barriers to enrollment of patients with LEP in research were unavailability of translated consent forms and increased time needed to enroll patients. Conclusions: Patients with LEP were 3.4 times less likely to participate in gynecologic oncology trials than fluent English speakers. De-aggregation of race, ethnicity, and language proficiency yielded important information about enrollment disparities. These findings offer avenues for future interventions to correct disparities.
Another New Beginning
Authors: Margaret Tempero
Journal: Journal of the National Comprehensive Cancer Network (2023)

Another New Beginning I have never quite figured out why we feel like we have a clean start each January.After all, the problems we were dealing with in December don't go away.Health problems, financial issues, interpersonal discord-they're all still there.Maybe after the holiday break we feel rested and more ready to cope with it all?Still, the tradition is absolutely true for me-every new year feels like a new beginning.And with that new start comes my usual attempt at making New Year's resolutions, which is then quite promptly followed by my not keeping them.I have a virtual attic full of old resolutions that never saw the light of day.Discarded resolutions include things like learning to play Debussy's "Prelude to the Afternoon of a Faun" on the piano, fitting again into my wedding dress, running a marathon-admittedly rather impossible goals for someone as "mature" as I am! So, I've decided that this year will be different.I am picking 5 goals that I know I can achieve and that will help me be a better oncologist.Drumroll
Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment
Authors: Saurabh Zanwar, Morie A. Gertz, Eli Muchtar
Journal: Journal of the National Comprehensive Cancer Network (2023)

Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index of suspicion, making a delay in diagnosis common, which contributes to the high early mortality seen in this disease. Establishing the diagnosis of AL amyloidosis requires the demonstration of tissue deposition of amyloid fibrils. A bone marrow biopsy and fat pad aspirate performed concurrently have a high sensitivity for the diagnosis of AL amyloidosis and negate the need for organ biopsies in most patients. An accurate diagnosis requires amyloid typing via additional testing, including tissue mass spectrometry. Prognostication for AL amyloidosis is largely driven by the organs impacted. Cardiac involvement represents the single most important prognostic marker, and the existing staging systems are driven by cardiac biomarkers. Apart from organ involvement, plasma cell percentage on the bone marrow biopsy, specific fluorescence in situ hybridization findings, age at diagnosis, and performance status are important prognostic markers. This review elaborates on the diagnostic testing and prognostication for patients with newly diagnosed AL amyloidosis.
Neoadjuvant Immunotherapy Leads to Major Response and Low Recurrence in Localized Mismatch Repair–Deficient Colorectal Cancer
Authors: Bin-Yi Xiao, Xuan Zhang, Tai-Yuan Cao, Dan-Dan Li, Wu Jiang, Ling-Heng Kong, Jing-Hua Tang, Kai Han, Chen-Zhi Zhang, Wei-Jian Mei, Jian Xiao, Zhi-Zhong Pan, Yun-Feng Li, Xiao-Shi Zhang, Pei-Rong Ding
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Our study aimed to evaluate the efficacy and feasibility of neoadjuvant anti–PD-1 treatment for localized mismatch repair–deficient (dMMR) colorectal cancer (CRC). Patients and Methods: The study cohort included patients with localized dMMR CRC who received PD-1 inhibitors as neoadjuvant therapy from 3 medical centers in Southern China. Main eligibility criteria included age between 18 and 75 years, ECOG performance status of 0 or 1, and receipt of ≥2 doses of PD-1 inhibitors. Results: A total of 73 patients were included. Most of the tumors were locally advanced, including 19 (26.0%) T4a and 29 (39.7%) T4b. Most patients (79.5%) received PD-1 inhibitor monotherapy. Objective response per radiologic assessment was achieved in 62 (84.9%) patients, including 17 (23.3%) with complete response (CR) and 45 (61.6%) with partial response, with a median time to response of 9.6 weeks. Patients with T4a/4b disease had a similar response rate as those with T2–3 disease (84.0% vs 85.4%; P =.999). As of writing, a total of 50 patients have undergone surgery. Pathologic CR was achieved in most (57.1%) patients and remained high (59.5%) even among the 38 patients with T4a/4b disease. The 17 patients with CR did not undergo surgery and adopted a watch-and-wait strategy. After a median follow-up of 17.2 months (range, 3.4–45.1 months), the overall median recurrence-free and overall survivals were not reached. Among patients undergoing surgery or achieving CR, the 2-year tumor-specific disease-free and overall survival rates were both 100%. During neoadjuvant treatment, grade 3–4 adverse events occurred in 8 patients; 4 required acute intervention. Severe postoperative complications were recorded in 4 patients, 3 of whom required a second surgery. Conclusions: Neoadjuvant therapy with PD-1 blockade is highly effective for localized dMMR CRC, with an acceptable safety profile and low recurrence rate. This treatment holds promise for becoming the new standard of care for localized dMMR CRCs.
Binding and neutralizing anti-AAV antibodies: Detection and implications for rAAV-mediated gene therapy
Authors: Martin Schulz, Daniel I. Levy, Christos J. Petropoulos, George Bashirians, Ian Winburn, Matthias Mahn, Suryanarayan Somanathan, Seng H. Cheng, Barry J. Byrne
Journal: Molecular Therapy (2023)

Assessment of anti-adeno-associated virus (AAV) antibodies in patients prior to systemic gene therapy administration is an important consideration regarding efficacy and safety of the therapy. Approximately 30%-60% of individuals have pre-existing anti-AAV antibodies. Seroprevalence is impacted by multiple factors, including geography, age, capsid serotype, and assay type. Anti-AAV antibody assays typically measure (1) transduction inhibition by detecting the neutralizing capacity of antibodies and non-antibody neutralizing factors, or (2) total anti-capsid binding antibodies, regardless of neutralizing activity. Presently, there is a paucity of head-to-head data and standardized approaches associating assay results with clinical outcomes. In addition, establishing clinically relevant screening titer cutoffs is complex. Thus, meaningful comparisons across assays are nearly impossible. Although complex, establishing screening assays in routine clinical practice to identify patients with antibody levels that may impact favorable treatment outcomes is achievable for both transduction inhibition and total antibody assays. Formal regulatory approval of such assays as companion diagnostic tests will confirm their suitability for specific recombinant AAV gene therapies. This review covers current approaches to measure anti-AAV antibodies in patient plasma or serum, their potential impact on therapeutic safety and efficacy, and investigative strategies to mitigate the effects of pre-existing anti-AAV antibodies in patients.
NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022
Authors: Craig Horbinski, Louis Burt Nabors, Jana Portnow, Joachim Baehring, Ankush Bhatia, Orin Bloch, Steven Brem, Nicholas Butowski, Donald M. Cannon, Samuel Chao, Milan G. Chheda, Andrew J. Fabiano, Peter Forsyth, Pierre Gigilio, Jona Hattangadi-Gluth, Matthias Holdhoff, Larry Junck, Thomas Kaley, Ryan Merrell, Maciej M. Mrugala, Seema Nagpal, Lucien A. Nedzi, Kathryn Nevel, Phioanh L. Nghiemphu, Ian Parney, Toral R. Patel, Katherine Peters, Vinay K. Puduvalli, Jason Rockhill, Chad Rusthoven, Nicole Shonka, Lode J. Swinnen, Stephanie Weiss, Patrick Yung Wen, Nicole E. Willmarth, Mary Anne Bergman, Susan Darlow
Journal: Journal of the National Comprehensive Cancer Network (2023)

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2–3 oligodendroglioma [1p19q codeleted, IDH- mutant], WHO grade 2–4 IDH- mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non–AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding molecular profiling of gliomas.
Indicators of Clinical Trajectory in Patients With Cancer Who Receive Cardiopulmonary Resuscitation
Authors: Sanjay Chawla, Cristina Gutierrez, Prabalini Rajendram, Kenneth Seier, Kay See Tan, Kara Stoudt, Marian Von-Maszewski, Jorge L. Morales-Estrella, Natalie T. Kostelecky, Louis P. Voigt
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Patients with cancer who require cardiopulmonary resuscitation (CPR) historically have had low survival to hospital discharge; however, overall CPR outcomes and cancer survival have improved. Identifying patients with cancer who are unlikely to survive CPR could guide and improve end-of-life discussions prior to cardiac arrest. Methods: Demographics, clinical variables, and outcomes including immediate and hospital survival for patients with cancer aged ≥18 years who required in-hospital CPR from 2012 to 2015 were collected. Indicators capturing the overall declining clinical and oncologic trajectory (ie, no further therapeutic options for cancer, recommendation for hospice, or recommendation for do not resuscitate) prior to CPR were determined a priori and manually identified. Results: Of 854 patients with cancer who underwent CPR, the median age was 63 years and 43.6% were female; solid cancers accounted for 60.6% of diagnoses. A recursive partitioning model selected having any indicator of declining trajectory as the most predictive factor in hospital outcome. Of our study group, 249 (29%) patients were found to have at least one indicator identified prior to CPR and only 5 survived to discharge. Patients with an indicator were more likely to die in the hospital and none were alive at 6 months after discharge. These patients were younger (median age, 59 vs 64 years; P ≤.001), had a higher incidence of metastatic disease (83.0% vs 62.9%; P &lt;.001), and were more likely to undergo CPR in the ICU (55.8% vs 36.5%; P &lt;.001) compared with those without an indicator. Of patients without an indicator, 145 (25%) were discharged alive and half received some form of cancer intervention after CPR. Conclusions: Providers can use easily identifiable indicators to ascertain which patients with cancer are at risk for death despite CPR and are unlikely to survive to discharge. These findings can guide discussions regarding utility of resuscitation and the lack of further cancer interventions even if CPR is successful.
Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer
Authors: Dirk Mehrens, Kristina K.M. Kramer, Lena M. Unterrainer, Leonie Beyer, Peter Bartenstein, Matthias F. Froelich, Fabian Tollens, Jens Ricke, Johannes Rübenthaler, Nina-Sophie Schmidt-Hegemann, Annika Herlemann, Marcus Unterrainer, Wolfgang G. Kunz
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Metastatic castration-resistant prostate cancer poses a therapeutic challenge with poor prognosis. The VISION trial showed prolonged progression-free and overall survival in patients treated with lutetium Lu 177 vipivotide tetraxetan ( 177 Lu-PSMA-617) radioligand therapy compared with using the standard of care (SoC) alone. The objective of this study was to determine the cost-effectiveness of 177 Lu-PSMA-617 treatment compared with SoC therapy. Methods: A partitioned survival model was developed using data from the VISION trial, which included overall and progression-free survival and treatment regimens for 177 Lu-PSMA-617 and SoC. Treatment costs, utilities for health states, and adverse events were derived from public databases and the literature. Because 177 Lu-PSMA-617 was only recently approved, costs for treatment were extrapolated from 177 Lu-DOTATATE. Outcome measurements included the incremental cost, effectiveness, and cost-effectiveness ratio. The analysis was performed in a US setting from a healthcare system perspective over the lifetime horizon of 60 months. The willingness-to-pay threshold was set to $50,000, $100,000, and $200,000 per quality-adjusted life years (QALYs). Results: The 177 Lu-PSMA-617 group was estimated to gain 0.42 incremental QALYs. Treatment using 177 Lu-PSMA-617 led to an increase in costs compared with SoC ($169,110 vs $85,398). The incremental cost, effectiveness, and cost-effectiveness ratio for 177 Lu-PSMA-617 therapy was $200,708/QALYs. Sensitivity analysis showed robustness of the model regarding various parameters, which remained cost-effective at all lower and upper parameter bounds. In probabilistic sensitivity analysis using Monte Carlo simulation with 10,000 iterations, therapy using 177 Lu-PSMA-617 was determined as the cost-effective strategy in 37.14% of all iterations at a willingness-to-pay threshold of $200,000/QALYs. Conclusions: Treatment using 177 Lu-PSMA-617 was estimated to add a notable clinical benefit over SoC alone. Based on the model results, radioligand therapy represents a treatment strategy for patients with metastatic castration-resistant prostate cancer with cost-effectiveness in certain scenarios.
A Survey of the National Comprehensive Cancer Network on Approaches Toward Addressing Patients’ Transportation Insecurity
Authors: Krisda H. Chaiyachati, Diana Krause, Jessica Sugalski, Evan M. Graboyes, Lawrence N. Shulman
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Addressing patients’ social determinants of health is a national priority for cancer treatment centers. Transportation insecurity is one major challenge for patients undergoing active cancer treatment, and missing treatments can result in worse cancer treatment outcomes, including worse morbidity and mortality. How cancer treatment centers are addressing transportation insecurity is understudied. Methods: In January and February 2022, the NCCN Best Practices Committee conducted a survey of NCCN’s 31 Member Institutions (currently 32 member institutions as of April 2022) to assess how centers were addressing patient transportation insecurity: how they screen for transportation insecurity, coordinate transportation, and fund transportation initiatives, and their plans to address transportation insecurity in the future. Results : A total of 25 of 31 (81%) NCCN Member Institutions responded to the survey, of which 24 (96%) reported supporting the transportation needs of their patients through screening, coordinating, and/or funding transportation. Patients’ transportation needs were most often identified by social workers (96%), clinicians (83%), or patients self-declaring their needs (79%). Few centers (33%) used routine screening approaches (eg, universal screening of social risk factors) to systematically identify transportation needs, and 54% used the support of technology platforms or a vendor to coordinate transportation. Transportation was predominantly funded via some combination of philanthropy (88%), grants (63%), internal dollars (63%), and reimbursement from insurance companies (58%). Over the next 12 months, many centers were either going to continue their current transportation programs in their current state (60%) or expand existing programs (32%). Conclusions: Many NCCN Member Institutions are addressing the transportation needs of their patients. Current efforts are heterogeneous. Few centers have systematic, routine screening approaches, and funding relies on philanthropy more so than institutional dollars or reimbursement from insurers. Opportunities exist to establish more structured, scalable, and sustainable programs for patients’ transportation needs.
Effectiveness of Simulation-Based Training on Transesophageal Echocardiography Learning
Authors: Théo Pezel, Julien Dreyfus, Basile Mouhat, Clémence Thébaut, Etienne Audureau, Anne Bernard, Yoan Lavie Badie, Yohann Bohbot, Damien Fard, Lee S. Nguyen, Cécile Monteil, Loïc Bière, Florent Le Ven, Marjorie Canu, Sophie Ribeyrolles, Baptiste Mion, Baptiste Bazire, Charles Fauvel, Jennifer Cautela, Théo Cambet, Thierry Le Tourneau, Erwan Donal, Stéphane Lafitte, Julien Magne, Nicolas Mansencal, Augustin Coisne, Samy Aghezzaf, Virginie Blanchard, Alexandra Meilhac
Journal: JAMA Cardiology (2023)

Trial Registration ClinicalTrials.gov Identifier: NCT05564507